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Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

ABSTRACT: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

SUBMITTER: Hofer E

PROVIDER: S-EPMC7508833 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

Hofer Edith E Roshchupkin Gennady V GV Adams Hieab H H HHH Knol Maria J MJ Lin Honghuang H Li Shuo S Zare Habil H Ahmad Shahzad S Armstrong Nicola J NJ Satizabal Claudia L CL Bernard Manon M Bis Joshua C JC Gillespie Nathan A NA Luciano Michelle M Mishra Aniket A Scholz Markus M Teumer Alexander A Xia Rui R Jian Xueqiu X Mosley Thomas H TH Saba Yasaman Y Pirpamer Lukas L Seiler Stephan S Becker James T JT Carmichael Owen O Rotter Jerome I JI Psaty Bruce M BM Lopez Oscar L OL Amin Najaf N van der Lee Sven J SJ Yang Qiong Q Himali Jayandra J JJ Maillard Pauline P Beiser Alexa S AS DeCarli Charles C Karama Sherif S Lewis Lindsay L Harris Mat M Bastin Mark E ME Deary Ian J IJ Veronica Witte A A Beyer Frauke F Loeffler Markus M Mather Karen A KA Schofield Peter R PR Thalamuthu Anbupalam A Kwok John B JB Wright Margaret J MJ Ames David D Trollor Julian J Jiang Jiyang J Brodaty Henry H Wen Wei W Vernooij Meike W MW Hofman Albert A Uitterlinden André G AG Niessen Wiro J WJ Wittfeld Katharina K Bülow Robin R Völker Uwe U Pausova Zdenka Z Bruce Pike G G Maingault Sophie S Crivello Fabrice F Tzourio Christophe C Amouyel Philippe P Mazoyer Bernard B Neale Michael C MC Franz Carol E CE Lyons Michael J MJ Panizzon Matthew S MS Andreassen Ole A OA Dale Anders M AM Logue Mark M Grasby Katrina L KL Jahanshad Neda N Painter Jodie N JN Colodro-Conde Lucía L Bralten Janita J Hibar Derrek P DP Lind Penelope A PA Pizzagalli Fabrizio F Stein Jason L JL Thompson Paul M PM Medland Sarah E SE Sachdev Perminder S PS Kremen William S WS Wardlaw Joanna M JM Villringer Arno A van Duijn Cornelia M CM Grabe Hans J HJ Longstreth William T WT Fornage Myriam M Paus Tomas T Debette Stephanie S Ikram M Arfan MA Schmidt Helena H Schmidt Reinhold R Seshadri Sudha S

Nature communications 20200922 1

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic ...[more]

PMID: 32963231

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Project description:Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral performance correlates of normative gray matter thinning during adolescence.

Project description:BackgroundAn important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear.AimsTo assess shared genetic liability and potential causal effects between schizophrenia and arrhythmic disorders and electrocardiogram (ECG) traits.MethodWe leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53 386 cases, 77 258 controls), arrhythmic disorders (atrial fibrillation, 55 114 cases, 482 295 controls; Brugada syndrome, 2820 cases, 10 001 controls) and ECG traits (heart rate (variability), PR interval, QT interval, JT interval and QRS duration, n = 46 952-293 051). We examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Bidirectional causal relations between schizophrenia and arrhythmic disorders and ECG traits were explored using Mendelian randomisation.ResultsThere was no evidence for global genetic correlation, except between schizophrenia and Brugada syndrome (rg = 0.14, 95% CIs = 0.06-0.22, P = 4.0E-04). In contrast, strong positive and negative local correlations between schizophrenia and all cardiac traits were found across the genome. In the most strongly associated regions, genes related to immune and viral response mechanisms were overrepresented. Mendelian randomisation indicated that liability to schizophrenia causally increases Brugada syndrome risk (beta = 0.14, CIs = 0.03-0.25, P = 0.009) and heart rate during activity (beta = 0.25, CIs = 0.05-0.45, P = 0.015).ConclusionsDespite little evidence for global genetic correlation, specific genomic regions and biological pathways emerged that are important for both schizophrenia and arrhythmia. The putative causal effect of liability to schizophrenia on Brugada syndrome warrants increased cardiac monitoring and early medical intervention in people with schizophrenia.

Dataset Information

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

Publications

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

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